Fish composition in the Guadiamar River basin after one of the worst mining spills in Europe

On 25 April 1998, the tailing pond of the Los Frailes mine in Aznalcollar (Seville, Spain) ruptured, causing one of the most harmful environmental disasters in Europe in recent decades. Through the crack, 6 hm3 of acidic water and metallic mud were spilt, defaunating a large area of the Guadiamar River. After the spill cleanup and habitat restoration, multiple anthropogenic impacts continued to degrade the affected area. This work aimed to provide the most updated list of fish species in the Guadiamar River basin after the spill. Data were collected between 1999 and 2011 by electrofishing, light-traps, minnow-traps and multimesh gill-nests in 78 sampling sites. Species richness values for both native and exotic species in the Guadiamar River basin were high when compared with values for other right bank tributaries of the Guadalquivir River. This may be due to direct contact with the mouth of the Guadalquivir, which allowed the presence of migratory species. It may also be due to its location in the lower part of the Guadalquivir River basin, where exotic species accumulated. Among the Guadiamar River basin species, Luciobarbus sclateri and Squalius alburnoides have the widest distribution. The former is a generalist species resistant to unfavourable habitat changes, and the latter has a very successful breeding strategy. However, when focused on the affected area, there was a marked increase in exotic species, and both pumpkinseed (Lepomis gibbosus) and carp (Cyprinus carpio) co-dominated together with the native L. sclateri and S. alburnoides. The distribution of species within the river basin suggests that the upper section (except the Agrio reservoir) and middle section tributaries may be acting as native species shelters, while the affected area becomes an exotic species source. This information should be useful for monitoring future changes in the species composition and for management planning measures

Habitat quality affects the condition of Luciobarbus sclateri in the Guadiamar River (SW Iberian Peninsula): Effects of disturbances by the toxic spill of the Aznalcóllar mine

This study analyzes the somatic condition of southern Iberian barbel Luciobarbus sclateri (Günther, 1868) in the Guadiamar River (SW Iberian Peninsula). This river was seriously affected by a toxic spill of about 4 million cubic meters of acidic water and 2 million cubic meters of mud rich in heavy metals. Once the spill removal works concluded, sites affected and unaffected by the accident were sampled to study its effects on the fish fauna. The ecological variables registered were related to water quality, physical state of reaches, ecological quality, resources exploited by fish, and potential intra-specific interactions. From an initial 15 ecological variables, seasonal water flow and pH explained most of the variation in barbel condition. This study shows that the Guadiamar River, 56 months after the accident, is still undergoing a recovery process where, beyond ecological variables, proximity to the affected area is the most influential factor for fish condition. © 2012 Springer Science+Business Media B.V

Improvement of infrared single-photon detectors absorptance by integrated plasmonic structures

Plasmonic structures open novel avenues in photodetector development. Optimized illumination configurations are reported to improve p-polarized light absorptance in superconducting-nanowire single-photon detectors (SNSPDs) comprising short- and long-periodic niobium-nitride (NbN) stripe-patterns. In OC-SNSPDs consisting of ~quarter-wavelength dielectric layer closed by a gold reflector the highest absorptance is attainable at perpendicular incidence onto NbN patterns in P-orientation due to E-field concentration at the bottom of nano-cavities. In NCAI-SNSPDs integrated with nano-cavity-arrays consisting of vertical and horizontal gold segments off-axis illumination in S-orientation results in polar-angle-independent perfect absorptance via collective resonances in short-periodic design, while in long-periodic NCAI-SNSPDs grating-coupled surface waves promote EM-field transportation to the NbN stripes and result in local absorptance maxima. In NCDAI-SNSPDs integrated with nano-cavity-deflector-array consisting of longer vertical gold segments large absorptance maxima appear in 3p-periodic designs due to E-field enhancement via grating-coupled surface waves synchronized with the NbN stripes in S-orientation, which enable to compensate fill-factor-related retrogression.United States. Dept. of Energy (Frontier Research Centers

Amphipathic DNA polymers exhibit antiviral activity against systemic Murine Cytomegalovirus infection

<p>Abstract</p> <p>Background</p> <p>Phosphorothioated oligonucleotides (PS-ONs) have a sequence-independent, broad spectrum antiviral activity as amphipathic polymers (APs) and exhibit potent in vitro antiviral activity against a broad spectrum of herpesviruses: HSV-1, HSV-2, HCMV, VZV, EBV, and HHV-6A/B, and in vivo activity in a murine microbiocide model of genital HSV-2 infection. The activity of these agents against animal cytomegalovirus (CMV) infections in vitro and in vivo was therefore investigated.</p> <p>Results</p> <p>In vitro, a 40 mer degenerate AP (REP 9) inhibited both murine CMV (MCMV) and guinea pig CMV (GPCMV) with an IC₅₀of 0.045 μM and 0.16 μM, respectively, and a 40 mer poly C AP (REP 9C) inhibited MCMV with an IC₅₀of 0.05 μM. Addition of REP 9 to plaque assays during the first two hours of infection inhibited 78% of plaque formation whereas addition of REP 9 after 10 hours of infection did not significantly reduce the number of plaques, indicating that REP 9 antiviral activity against MCMV occurs at early times after infection. In a murine model of CMV infection, systemic treatment for 5 days significantly reduced virus replication in the spleens and livers of infected mice compared to saline-treated control mice. REP 9 and REP 9C were administered intraperitoneally for 5 consecutive days at 10 mg/kg, starting 2 days prior to MCMV infection. Splenomegaly was observed in infected mice treated with REP 9 but not in control mice or in REP 9 treated, uninfected mice, consistent with mild CpG-like activity. When REP 9C (which lacks CpG motifs) was compared to REP 9, it exhibited comparable antiviral activity as REP 9 but was not associated with splenomegaly. This suggests that the direct antiviral activity of APs is the predominant therapeutic mechanism <it>in vivo</it>. Moreover, REP 9C, which is acid stable, was effective when administered orally in combination with known permeation enhancers.</p> <p>Conclusion</p> <p>These studies indicate that APs exhibit potent, well tolerated antiviral activity against CMV infection in vivo and represent a new class of broad spectrum anti-herpetic agents.</p

Randomized pilot study to disseminate caries-control services in dentist offices

BACKGROUND: To determine whether education and financial incentives increased dentists' delivery of fluoride varnish and sealants to at risk children covered by capitation dental insurance in Washington state (U.S.). METHODS: In 1999, 53 dental offices in Washington Dental Service's capitation dental plan were invited to participate in the study, and consenting offices were randomized to intervention (n = 9) and control (n = 10) groups. Offices recruited 689 capitation children aged 6–14 and at risk for caries, who were followed for 2 years. Intervention offices received provider education and fee-for-service reimbursement for delivering fluoride varnish and sealants. Insurance records were used to calculate office service rates for fluoride, sealants, and restorations. Parents completed mail surveys after follow-up to measure their children's dental utilization, dental satisfaction, dental fear and oral health status. Regression models estimated differences in service rates between intervention and control offices, and compared survey measures between groups. RESULTS: Nineteen offices (34%) consented to participate in the study. Fluoride and sealant rates were greater in the intervention offices than the control offices, but the differences were not statistically significant. Restoration rates were lower in the intervention offices than the control offices. Parents in the intervention group reported their children had less dental fear than control group parents. CONCLUSION: Due to low dentist participation the study lacked power to detect an intervention effect on dentists' delivery of caries-control services. The intervention may have reduced children's dental fear

Discovery of Diverse Small Molecule Chemotypes with Cell-Based PKD1 Inhibitory Activity

Protein kinase D (PKD) is a novel family of serine/threonine kinases regulated by diacylglycerol, which is involved in multiple cellular processes and various pathological conditions. The limited number of cell-active, selective inhibitors has historically restricted biochemical and pharmacological studies of PKD. We now markedly expand the PKD1 inhibitory chemotype inventory with eleven additional novel small molecule PKD1 inhibitors derived from our high throughput screening campaigns. The in vitro IC50s for these eleven compounds ranged in potency from 0.4 to 6.1 µM with all of the evaluated compounds being competitive with ATP. Three of the inhibitors (CID 1893668, (1Z)-1-(3-ethyl-5-methoxy-1,3-benzothiazol-2-ylidene)propan-2-one; CID 2011756, 5-(3-chlorophenyl)-N-[4-(morpholin-4-ylmethyl)phenyl]furan-2-carboxamide; CID 5389142, (6Z)-6-[4-(3-aminopropylamino)-6-methyl-1H-pyrimidin-2-ylidene]cyclohexa-2,4-dien-1-one) inhibited phorbol ester-induced endogenous PKD1 activation in LNCaP prostate cancer cells in a concentration-dependent manner. The specificity of these compounds for PKD1 inhibitory activity was supported by kinase assay counter screens as well as by bioinformatics searches. Moreover, computational analyses of these novel cell-active PKD1 inhibitors indicated that they were structurally distinct from the previously described cell-active PKD1 inhibitors while computational docking of the new cell-active compounds in a highly conserved ATP-binding cleft suggests opportunities for structural modification. In summary, we have discovered novel PKD1 inhibitors with in vitro and cell-based inhibitory activity, thus successfully expanding the structural diversity of small molecule inhibitors available for this important pharmacological target

Engineering of Three-Finger Fold Toxins Creates Ligands with Original Pharmacological Profiles for Muscarinic and Adrenergic Receptors

Protein engineering approaches are often a combination of rational design and directed evolution using display technologies. Here, we test “loop grafting,” a rational design method, on three-finger fold proteins. These small reticulated proteins have exceptional affinity and specificity for their diverse molecular targets, display protease-resistance, and are highly stable and poorly immunogenic. The wealth of structural knowledge makes them good candidates for protein engineering of new functionality. Our goal is to enhance the efficacy of these mini-proteins by modifying their pharmacological properties in order to extend their use in imaging, diagnostics and therapeutic applications. Using the interaction of three-finger fold toxins with muscarinic and adrenergic receptors as a model, chimeric toxins have been engineered by substituting loops on toxin MT7 by those from toxin MT1. The pharmacological impact of these grafts was examined using binding experiments on muscarinic receptors M1 and M4 and on the α1A-adrenoceptor. Some of the designed chimeric proteins have impressive gain of function on certain receptor subtypes achieving an original selectivity profile with high affinity for muscarinic receptor M1 and α1A-adrenoceptor. Structure-function analysis supported by crystallographic data for MT1 and two chimeras permits a molecular based interpretation of these gains and details the merits of this protein engineering technique. The results obtained shed light on how loop permutation can be used to design new three-finger proteins with original pharmacological profiles

A systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma

BACKGROUND: Fractionated plasma metanephrine measurements are commonly used in biochemical testing in search of pheochromocytoma. METHODS: We aimed to critically appraise the diagnostic efficacy of fractionated plasma free metanephrine measurements in detecting pheochromocytoma. Nine electronic databases, meeting abstracts, and the Science Citation Index were searched and supplemented with previously unpublished data. Methodologic and reporting quality was independently assessed by two endocrinologists using a checklist developed by the Standards for Reporting of Diagnostic Studies Accuracy Group and data were independently abstracted. RESULTS: Limitations in methodologic quality were noted in all studies. In all subjects (including those with genetic predisposition): the sensitivities for detection of pheochromocytoma were 96%–100% (95% CI ranged from 82% to 100%), whereas the specificities were 85%–100% (95% CI ranged from 78% to 100%). Statistical heterogeneity was noted upon pooling positive likelihood ratios when those with predisposition to disease were included (p < 0.001). However, upon pooling the positive or negative likelihood ratios for patients with sporadic pheochromocytoma (n = 191) or those at risk for sporadic pheochromocytoma (n = 718), no statistical heterogeneity was noted (p = 0.4). For sporadic subjects, the pooled positive likelihood ratio was 5.77 (95% CI = 4.90, 6.81) and the pooled negative likelihood ratio was 0.02 (95% CI = 0.01, 0.07). CONCLUSION: Negative plasma fractionated free metanephrine measurements are effective in ruling out pheochromocytoma. However, a positive test result only moderately increases suspicion of disease, particularly when screening for sporadic pheochromocytoma